Relapsing experimental allergic encephalomyelitis (R-EAE) resembles more closely the human disease, multiple sclerosis, both clinically and pathologically. From the first clinical relapse and thereafter, recurrent demyelination becomes the leading pathological change in this model, but its pathogenesis is at present unresolved. R-EAE can be induced in Strain 13 and Hartley guinea pigs by sensitization with homologous CNS tissue or myelin. Since immunization with MBP fails to induce the disease, myelin secondary antigen(s) are thought to be instrumental in the clinical relapses and recurrent demyelination of R-EAE. Preliminary studies indicate that sensitization of animals with ether:ethanol extracted homologous myelin, which contains only the myelin proteins, most sulfolipids and gangliosides, can also induce relapses. It is the purpose of this study to search and identify the secondary antigen(s) by bioassaying various recombinations of myelin proteins and lipids.